Treatment with oral anticoagulant therapy entails a delicate balance between over( risk of bleeding) and under- (risk of thrombemboli) anticoagulation. Therapy is therefore monitored to maintain its anticoagulant effect within a narrow range. The main aim of this research was to determine the optimal intensity of long-term anticoagulant therapy in 3404 post-myocardial infarction patients. Chapter 1 gives a review of long-term clinical trials which assessed the mertts of anticoagulant therapy in the secondary prevention of morbidity and mortality after myocardial infarction. This review includes the results of more than thirty trials reported in the literature in the past forty years, however, unpublished data or results of small trials, were not considered. Few of these trials were randomized, and the level of anticoagulation was properly maintained in only some of these studies. The results of most of these trials have failed to convincingly demonstrate the beneficial effects of long-term anticoagulant therapy as a secondary preventive measure and the use of such therapy has therefore remained controversial. Chapters 2 and 3 describe the design and execution of the ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. The main results of this trial are submitted in Appendix-A. ASPECT was designed to be a randomized, double-blind, placebo controlled, multicentre trial which compared standard oral anticoagulant therapy with placebo with regards to mortality and cardiovascular events. Chapter 2 describes the design and procedures of the ASPECT trial in detail, in particular the methods for double-blind anticoagulant titration. Chapter 3 presents an outline of the data processing system as used in ASPECT. A standardized procedure which was developed for data handling insured a high level of data quality derived from the participating centres. Chapters 4, 5 and 6 addresses the effectiveness and safety of oral anticoagulant therapy. Chapter 4 reviews various methods, previously described, to evaluate therapeutic achievement of anticoagulant therapy in the ASPECT trial. In Chapter 5, the optimal achieved intensity of anticoagulant therapy required to prevent recurrence of arterial thromboembolic and haemorrhagic complications was quantitatively evaluated with regard to the international normalized ratio (INR) intensity preceding the event, enabling the calculation of INR-specific incidence rates. The INR expresses the level of anticoagulant therapy in an internationally agreed term. It is the common term for the prothrombin time as measured in a patient on oral anticoagulant therapy. Chapter 6 gives a detailed description of the risk of stroke in the ASPECT population. Finally, a discussion of the findings is provided in Chapter 7, followed by recommendations for further research

J.R.T.C. Roelandt (Jos)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Azar, A.J. (1993, May 26). Therapeutic achievement with long-term oral anticoagulants in post-myocardial infarction patients. Erasmus University Rotterdam. Retrieved from